Genetic Variant MAN1C1:c.1047+198G>T (chr1-25758907-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020379.4(MAN1C1):c.1047+198G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 584,942 control chromosomes in the GnomAD database, including 1,667 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.079 ( 538 hom., cov: 32)

Exomes 𝑓: 0.064 ( 1129 hom. )

Consequence

MAN1C1
NM_020379.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

2 publications found

Variant links:

Genes affected

MAN1C1 (HGNC:19080): (mannosidase alpha class 1C member 1) Predicted to enable mannosyl-oligosaccharide 1,2-alpha-mannosidase activity. Predicted to be involved in N-glycan processing. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN1C1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4 link	c.1047+198G>T		intron_variant	Intron 6 of 11	ENST00000374332.9	NP_065112.1	Q9NR34Q59G34

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAN1C1	ENST00000374332.9 link	c.1047+198G>T	intron_variant	Intron 6 of 11	1	NM_020379.4	ENSP00000363452.4	Q9NR34
MAN1C1	ENST00000473891.1 link	n.643G>T	non_coding_transcript_exon_variant	Exon 5 of 5	4
MAN1C1	ENST00000263979.7 link	c.507+198G>T	intron_variant	Intron 7 of 12	5		ENSP00000263979.3	B1AJZ5
MAN1C1	ENST00000374329.1 link	c.360+198G>T	intron_variant	Intron 5 of 10	2		ENSP00000363449.1	A6NGN6

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

12012

AN:

151934

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0784

GnomAD4 exome

AF:

0.0642

AC:

27811

AN:

432890

Hom.:

1129

Cov.:

AF XY:

0.0613

AC XY:

14050

AN XY:

229226

show subpopulations

African (AFR)

AF:

0.116

AC:

1405

AN:

12164

American (AMR)

AF:

0.0389

AC:

732

AN:

18822

Ashkenazi Jewish (ASJ)

AF:

0.0800

AC:

1046

AN:

13070

East Asian (EAS)

AF:

0.0000679

AC:

AN:

29476

South Asian (SAS)

AF:

0.0207

AC:

955

AN:

46190

European-Finnish (FIN)

AF:

0.0651

AC:

1807

AN:

27740

Middle Eastern (MID)

AF:

0.0666

AC:

205

AN:

3076

European-Non Finnish (NFE)

AF:

0.0774

AC:

19937

AN:

257418

Other (OTH)

AF:

0.0691

AC:

1722

AN:

24934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1194

2387

3581

4774

5968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0791

AC:

12020

AN:

152052

Hom.:

538

Cov.:

AF XY:

0.0751

AC XY:

5585

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.111

AC:

4595

AN:

41510

American (AMR)

AF:

0.0526

AC:

804

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0888

AC:

308

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0147

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0607

AC:

644

AN:

10614

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0787

AC:

5338

AN:

67828

Other (OTH)

AF:

0.0776

AC:

164

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

584

1169

1753

2338

2922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0800

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.55

(source)

DANN

Benign

0.55

PhyloP100

-0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over